Product Distribution Control for Glucosamine Condensation: Nuclear Magnetic Resonance (NMR) Investigation Substantiated by Density Functional Calculations

Selective conversion of glucosamine (GlcNH<sub>2</sub>) to deoxyfructosazine (DOF) and fructosazine (FZ) with additives was investigated. Significantly enhanced yield of DOF can be improved to 40.2% with B­(OH)<sub>3</sub> as the additive. Chemical shift titration (via one-dimensional nuclear magnetic resonance (1D <sup>1</sup>H and <sup>13</sup>C NMR)) and two-dimensional nuclear magnetic resonance (2D NMR) including <sup>1</sup>H–<sup>13</sup>C HSQC and <sup>1</sup>H–<sup>1</sup>H COSY are used to investigate intermolecular interactions between B­(OH)<sub>3</sub> and GlcNH<sub>2</sub>. Diffusion-ordered NMR spectroscopy (DOSY) was further employed to identify intermediate species. Mechanistic investigation by NMR combined with electron spray ionization–mass spectroscopy (ESI-MS) discloses that a mixed 1:1 boron complex was identified as the major species, shedding light on the promotional effects of B­(OH)<sub>3</sub>, which is substantiated by density functional theory (DFT). Boron coordination effects make ring-opening and subsequent dehydration reaction thermodynamically and kinetically more favorable. Dehydration of dihydrofructosazine is a key step in controlling overall process (49.7 kcal/mol). Interestingly, chelating effect results in substantial reduction of this free-energy barrier (31.5 kcal/mol). Notably, FZ was gradually becoming the main product (yield up to 25.3%), with H<sub>2</sub>O<sub>2</sub> as the oxidant.